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Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic Lupus erythematosus

Colasanti, Tania and Maselli, Angela and Conti, Fabrizio and Sanchez, Massimo and Alessandri, Cristiano and Barbati, Cristiana and Vacirca, Davide and Tinari, Antonella and Chiarotti, Flavia and Giovannetti, Antonello and Franconi, Flavia and Valesini, Guido and Malorni, Walter and Pierdominici, Marina and Ortona, Elena (2012) Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic Lupus erythematosus. Arthritis & Rheumatism, Vol. 64 (3), p. 778-787. eISSN 1529-0131. Article.

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DOI: 10.1002/art.33400

Abstract

Objective. Estrogens influence many physiologic processes and are also implicated in the development or progression of numerous diseases, including autoimmune disorders. Aberrations of lymphocyte homeostasis that lead to the production of multiple pathogenic autoantibodies, including autoantibodies specific to estrogen receptor (ER), have been detected in the peripheral blood of patients with systemic lupus erythematosus (SLE). This study was undertaken to assess the presence of both anti-ERα and anti-ERβ antibodies in sera from patients with SLE, to analyze the effect of these antibodies on peripheral blood T lymphocyte homeostasis, and to evaluate their role as determinants of disease pathogenesis and progression.
Methods. Anti-ER antibody serum immunoreactivity was analyzed by enzyme-linked immunosorbent assay in samples from 86 patients with SLE and 95 healthy donors. Phenotypic and functional analyses were performed by flow cytometry and Western blotting.
Results. Anti-ERα antibodies were present in 45% of the patients with SLE, whereas anti-ERβ antibodies were undetectable. In healthy donors, anti-ERα antibodies induced cell activation and consequent apoptotic cell death in resting lymphocytes as well as proliferation of anti-CD3–stimulated T lymphocytes. A significant association between anti-ERα antibody values and clinical parameters, i.e., the SLE Disease Activity Index and arthritis, was found.
Conclusion. Our data suggest that anti-ERα autoantibodies interfere with T lymphocyte homeostasis and are significantly associated with lupus disease activity.

Item Type:Article
ID Code:7564
Status:Published
Refereed:Yes
Uncontrolled Keywords:Estrogen receptor (ER) α, T lymphocyte homeostasis, Systemic Lupus Erythematosus (SLE)
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > National laboratory of the national institute of biostructures and biosystems, Osilo
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Wiley
eISSN:1529-0131
Copyright Holders:© 2012, American College of Rheumatology
Deposited On:14 May 2012 09:34

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